Mixed tumors of the skin are characterized by a proliferation of epithelial cells embedded in a mesenchymal matrix with a wide spectrum of histologic appearances. The characterization of the extracellular matrix components of mixed tumors of the skin has so far received little attention. We performed an immunohistochemical study of type IV collagen, laminin, fibronectin, and tenascin distribution in a series of 10 mixed tumors of the skin. Laminin localized at the basement membrane around solid epithelial nests and tubulo-alveolar structures, whereas type IV collagen, fibronectin, and tenascin were also expressed in the myxoid stroma. Tenascin and fibronectin localized in the chondroid matrix. The extracellular matrix components were prominently expressed in mixed tumors of the skin, suggesting that they could play an important role in the formation and organization of myxoid and chondroid matrices and in the epithelial-mesenchymal interactions of these tumors.